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PubMed1989

The effects of prolonged ketamine-xylazine intravenous infusion on arterial blood pH, blood gases, mean arterial blood pressure, heart and respiratory rates, rectal temperature and reflexes in the rabbit.

The prolonged and safe maintenance of general anesthesia in rabbits with commonly used injectable agents is difficult. Protracted, stable anesthesia with short recovery time has been described in humans using continuous intravenous infusion of ketamine with or without sedatives, muscle relaxants and paralytics. This study evaluated the anesthetic plane achieved and respiratory and cardiovascular effects produced with a ketamine-xylazine intravenous infusion in New Zealand White rabbits. Ten female rabbits were anesthetized with intramuscularly administered ketamine hydrochloride (35 mg/kg) and xylazine hydrochloride (5 mg/kg) after the preanesthetic, baseline measurements of arterial blood pO2, pCO2 and pH and heart and respiratory rates were recorded. The above parameters as well as mean arterial blood pressure, righting, palpebral, pedal, and jaw reflexes were monitored ten minutes after the intramuscularly administered dosage and throughout 4 hours of infusion. Results showed moderate hypotension (21.2% deviation from normal, p less than 0.008) and profound hypoxemia (45% deviation from baseline, p less than 0.001) 10 minutes after the intramuscularly administered induction dosage. Then, the 4 hour infusion of ketamine (1 mg/minute) and xylazine (0.1 mg/minute) was started. Hypotension progressed (49.1% deviation from normal, p less than 0.008), but hypoxemia and hypercarbemia gradually improved with no resultant change (p greater than 0.1) in arterial pH. There was no significant change (p greater than 0.1) in respiratory rate but varying qualities of respiration were observed. Both mean arterial pO2 and pCO2 values returned to baseline within 20 minutes after completion of infusion. Heart rate and rectal temperature remained stable during the trial. The righting reflex was abolished in all rabbits throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed2000

Pharmacokinetics and safety of single intravenous infusions of the adenosine agonist, AMP 579, in patients with end-stage renal insufficiency.

The pharmacokinetics of an adenosine agonist (AMP 579) were characterized in patients with end-stage renal disease compared to sex- and age-matched healthy volunteers. All study participants were administered single AMP 579 doses of 50 micrograms/kg as a 6-hour, constant-rate intravenous infusion. Serial blood samples were obtained for measurement of plasma AMP 579 concentration, and predose samples were collected for determination of AMP 579 plasma protein binding. The safety of AMP 579 administration in renally impaired patients also was evaluated. AMP 579 was rapidly cleared from the systemic circulation in all subjects as plasma concentrations were below the limit of detection by 2 to 4 hours after terminating the infusion. Noncompartmental analysis yielded mean values for the plasma AMP 579 concentration at the end of the 6-hour infusion (C6 h) of 9.6 and 10.5 ng/mL and for systemic clearances (Cl) of 0.91 and 0.72 L/h/kg in renally impaired patients and healthy volunteers, respectively. Mean volumes of distribution (Vss) in the renally impaired and healthy volunteers were 0.92 and 0.84 L/kg, and terminal elimination half-life values (t1/2) were 1.61 and 1.33 hours, respectively. The extent to which AMP 579 is bound to plasma protein was not altered in renally impaired patients since the free fractions were 4.0% and 3.4% for renally impaired and healthy volunteers, respectively. It was concluded that the pharmacokinetic parameters of AMP 579 were similar in both groups. The 6-hour AMP 579 infusion was generally well tolerated by both renal patients and healthy volunteers. There were no serious adverse events, and there were only two mild adverse events in 1 renally impaired patient judged possibly related to the study drug that quickly resolved. There were no clinically significant changes in laboratory values or clinical evaluations during the study. There was a slight increase in heart rate during the infusion of similar magnitude for both the renal patients and healthy volunteers. These data suggest that AMP 579 may be administered to renally impaired patients with minimal cardiovascular effects and adverse events. These results in end-stage renal patients (worst-case scenario) indicate that dose adjustment in patients with renal insufficiency of any degree is not indicated in future studies of AMP 579.

Adult↗
PubMed2005

Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal models of cerebral ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34-, and CD45-) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce cerebral infarction volume and improve functional outcome.

Animals↗
PubMed2005

Volume expansion and plasma protein clearance during intravenous infusion of 5% albumin and autologous plasma.

Autologous plasma may be used to replace plasma volume and plasma proteins during surgery, but its effectiveness is largely unknown. In the present study, the characteristics of predonated frozen and thawed autologous plasma were compared with those of 5% albumin in 15 male volunteers who received 10 ml/kg of body weight of these colloids as intravenous infusions over 30 min. Venous blood was sampled and urine was collected over 8 h to outline the volume expansion and blood-interstitial fluid space transport of three plasma proteins (albumin, fibrinogen and antithrombin) by means of mass balance analysis. The maximum plasma dilution of 5% albumin and autologous plasma averaged 17 and 21% respectively, and their half-lives were 2.5 and 2.9 h respectively (P<0.03). The between-subject variability in dilution was most pronounced for autologous plasma. Transport of protein from blood to the interstitial space occurred faster when the infused fluid contained the protein in question. The rate was highest at 60 min, and the process was still in progress at 8 h when approx. 60% of the infused albumin, 45% of the fibrinogen and 75% of the infused antithrombin had been translocated to the interstitial fluid space. In contrast with the proteins, excess plasma water was removed by urinary excretion. It is concluded that the volume expansion is equivalent for the two colloid fluids, although it is more predictable for 5% albumin. The transport of protein outlasted the volume expansion.

Adult↗
PubMed2006

Effects of an intravenous infusion of Ringer's solution on eruption rates of incisor teeth in anesthetized rats.

OBJECTIVE: The vasculature within the socket is reportedly involved in determining the position of continuously erupting teeth. Thus, loss of body fluid in anesthetized rats, which would affect the vascular physiology, should influence tooth movement. We investigated the effects of an infusion of Ringer's solution on the systemic arterial blood pressure, regional blood flow at the base of the incisor, and axial tooth movement in anesthetized rats to determine the cause of tooth displacement. MATERIAL AND METHODS: In the experimental group, the animals received intravenous infusions of Ringer's solution at 27 microl/min for 13 h. In the control group, the animals did not receive the infusion. RESULTS: The infusion of Ringer's solution suppressed an increase of the mean arterial blood pressure from 86 to 80 mmHg and a decrease of the regional blood flow from 170 to 217 mV, and increased the eruption rate from 267 to 361 microm/13 h during the experimental period. There was a positive correlation between the eruption rate and regional blood flow, and a negative correlation between the blood pressure and regional blood flow. CONCLUSIONS: These results suggest that an infusion of Ringer's solution can cause an increase in the regional blood flow, resulting in increased fluid volume, elevated intra-socket pressure, and increased eruptive movement. It is possible that the regional vascular volume and/or pressure within the socket play an important role in determining the position of the incisor.

Animals↗
PubMed2004

Phase I and pharmacokinetic study of TZT-1027, a novel synthetic dolastatin 10 derivative, administered as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory cancer.

BACKGROUND: TZT-1027 is a synthetic dolastatin 10 analog with antineoplastic properties in various cell lines and tumor xenografts. The purpose of this phase I study was to evaluate the safety and toxicity, maximum tolerated dose, pharmacokinetics and pharmacodynamics, clinical and metabolic antitumor activity of TZT-1027 when given as a 1-h intravenous infusion every 3 weeks in patients with refractory solid tumors. PATIENTS AND METHODS: Patients had a histologically verified refractory tumor with measurable disease, were > or = 18 years old, had an Eastern Cooperative Oncology Group performance status <2 and adequate bone marrow, liver, renal and cardiac function. Dose-limiting toxicity was defined as platelets <25 x 10(9)/l, neutrophils <0.5 x 10(9)/l for >5 days, febrile neutropenia > or = 38.5 degrees C with grade 4 (National Cancer Institute-common toxicity criteria) neutropenia, or grade 3/4 non-hematological toxicity excluding nausea and vomiting. The last dose was the dose where > or = 2 out of six patients experienced dose-limiting toxicity in cycle one. The maximum tolerated dose was one dose level below with less than two of six patients with dose-limiting events. RESULTS: Twenty-one non-selected, fully evaluable patients were enrolled. The majority were male (19) and the median age was 55 years (range 39-67). Dose levels of TZT-1027 ranged from 1.35 to 3.0 mg/m(2). The median number of cycles was two (range 1-4). Dose-limiting toxicities were observed in three patients at the 3.0 mg/m(2) dose level, including neutropenia, fatigue and a short lasting, reversible peripheral neurotoxic syndrome. The most common toxicities per patient were fatigue, anorexia, alopecia, nausea, constipation, leukopenia and neutropenia. Based on RECIST criteria, the best response was stable disease in seven patients. The pharmacokinetic evaluation revealed a T(1/2) of approximately 7 h and linear kinetics. CONCLUSIONS: The recommended dose of TZT-1027 for the 3-weekly administration is 2.7 mg/m(2). Neutropenia, fatigue and a reversible peripheral neurotoxic syndrome are dose-limiting with this schedule. TZT-1027 may be associated with neurological side-effects in patients previously exposed to neurotoxic compounds such as oxaliplatin.

Adult↗
PubMed1990

Postoperative analgesia in children: a prospective study in intermittent intramuscular injection versus continuous intravenous infusion of morphine.

Few advancements in postoperative pain control in children have been made despite longstanding inadequacies in conventional intramuscular analgesic regimens. While overestimating narcotic complication rates, physicians often underestimate efficacious doses, nurses are reluctant to give injections, and many children in pain shy away from shots. This study prospectively focuses on the safety, efficacy, and complication rate of intermittent intramuscular (IM) versus continuous intravenous infusion (IV) of morphine sulfate (MS) in 46 nonventilated children following major chest, abdominal, or orthopedic surgical procedures. Twenty patients assigned to the IM group had a mean age of 6.17 years and a mean weight of 23.0 kg. Twenty-six patients assigned to the IV group had a mean age of 8.74 years and a mean weight of 27.4 kg. The mean IM MS dose was 12.3 micrograms/kg/h while the mean IV dose was 19.8 micrograms/kg/h (P less than .001). Postoperative pain was assessed with a linear analogue scale from 1 to 10 (1, "doesn't hurt"; 10, "worst hurt possible") for 3 days following operation. Using the analysis of covariance (ANACOVA), nurse, parent, and patient mean pain scores in the IV group were significantly lower than those of the IM group when controlled for age, MS dose, and complications (P less than .007). Nurse assessment of pain correlated well with the patient and parent assessments (Pearson correlation coefficients greater than 0.6). Not only did IV infusion give better pain relief than IM injections, but there were no major complications such as respiratory depression. Minor complications in this study (nausea, urinary retention, drowsiness, vomiting, hallucinations, lightheadedness, and prolonged ileus) were not significantly different between IM and IV groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1982

Compatibility of propranolol hydrochloride injection with intravenous infusion fluids in plastic containers.

The visual and chemical compatibility of propranolol hydrochloride injection admixtures in large-volume parenteral solutions (LVPs) packaged in plastic containers was studied. Propranolol hydrochloride injection was mixed with five different LVPs manufactured by three suppliers and packaged in plastic containers. Two concentrations (0.5 and 20 micrograms/ml) were tested. Samples were obtained via administration sets with 0.2-micron final filters. Visual appearance, pH, and propranolol hydrochloride concentration (HPLC method) of the admixtures were evaluated at 0, 4, 8, and 24 hours after preparation at room temperature and with ambient lighting. No change in visual appearance was observed. The pH of the admixtures ranged from 3.9 to 6.4, depending on the composition of the intravenous infusion fluid and propranolol hydrochloride concentration. There was no significant loss in potency during the test period. Additionally, there was no adsorption of propranolol hydrochloride onto the surface of polyvinyl chloride bags or polyolefin containers, or onto the filters. Propranolol hydrochloride can be mixed with common intravenous infusion fluids for 24 hours without compatibility problems when administered under normal conditions.

Drug Incompatibility↗
PubMed1988

Short-term effects of an intravenous infusion of a nutrient solution containing amino acids, glucose and insulin on leucine turnover and amino acid metabolism in patients with liver failure.

Tolerance to an intravenous nutrient infusion containing amino acids, glucose and insulin was assessed in 12 adult patients with clinical and biochemical evidence of liver failure. In six individuals, fasting plasma amino acid patterns and turnover rates were measured by a constant intravenous infusion of [1-14C]leucine tracer. In the remaining patients the same measurements were made after a 10 h intravenous infusion of a 'standard' commercial mixture of amino acids (3.4 g/h), dextrose (20 g/h) and insulin (1.6 units/h). On the second day, conditions were crossed over and measurements were repeated. With the exception of glycine, the infusion of the amino acid-containing solution failed to significantly increase plasma amino acid content. Plasma leucine flux measurements indicated that the explanation involved a reduction in input of amino acids derived from the breakdown of body proteins rather than an increased uptake of amino acids into protein; i.e., the rate of liberation of leucine from protein decreased by an average of 2.4 mmol/h (P less than 0.05) whilst intake only added 1.6 mmol/h. No consistent changes in encephalopathy were observed. In conclusion, the infusion of the amino acid solution together with glucose and insulin resulted in improved nutritional intake and had no deleterious short-term effects on encephalopathy. However, judging from the plasma amino acid concentrations, the composition of the commercial mixture could be improved by reducing the glycine content.

Amino Acids↗
PubMed1992

[Dynamics of bioelectric activity of the brain and erythrocyte ultrastructure after intravenous infusion of sodium bicarbonate to oncologic patients].

23 patients with malignant tumors of different location and histogenesis were investigated. There were no metastases in 9 cases. 10 patients had metastases in regional areas and 4--distant. The results were compared with those obtained in 4 patients with nonmalignant diseases. EEG, blood gases, plasma acid--base balance and ultrastructure of erythrocytes were explored before and after intravenous infusion of 4.2% sodium bicarbonate solution. The metabolic alkalosis induced amelioration of EEG, which was changed basically, the condense of pre-membrane layer disappeared or decreased in erythrocytes, and disaggregation of erythrocytes took place in cancer patients vs those with nonmalignant tumors. The results confirm the suggestion of generalized intracellular acidosis in malignant tumor patients. This acidosis can be temporarily avoided or diminished artificially by blood alkalosis.

Acidosis↗
PubMed1992

Relationship between glutathione content in liver and glutathione conjugation rate in the rat in vivo. Effect of buthionine sulphoximine pretreatment on conjugation of the two 2-bromoisovalerylurea enantiomers during intravenous infusion.

The relationship between hepatic glutathione content and hepatic glutathione conjugation rate in the rat in vivo was investigated. As substrate for glutathione conjugation, racemic (R,S)-2-bromoisovalerylurea (BIU) was used which gives rise to the biliary excretion of two diastereoisomeric glutathione conjugates and the urinary excretion of two diastereoisomeric mercapturates. The excretion rate of the glutathione conjugate in bile reflects hepatic conjugation exclusively. An intravenous infusion of BIU was given and the excretion rates of the metabolites in bile and urine were determined. The glutathione concentration in the liver was followed by taking biopsies every hour. Glutathione was depleted by the infused substrate; in rats that were pretreated with the inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO), the depletion of the glutathione content was more rapid. The rate of excretion of the glutathione conjugate in bile was plotted against hepatic glutathione content. These results indicate that the 'organ Km' for glutathione in the liver is approximately 0.5 mumol/g of liver, so that the hepatic glutathione conjugation rate is decreased only at severe glutathione depletion.

Acetylcysteine↗
PubMed1975

Septicaemia from prolonged intravenous infusions.

Four cases of septicaemia in children were traced to contaminated intravenous infusions and volume control sets. In each case Pseudomonas cepacia was isolated from multiple blood cultures and from intravenous fluid within the volume control set. The first patient died of septicaemia after a long and complicated postoperative period. The other three patients received appropriate antibiotics after removal of the contaminated intravenous sets and they recovered within 2 weeks.

Ampicillin↗
PubMed2001

High-dose intravenous infusion of irrigating fluids containing glycine and mannitol in the pig.

BACKGROUND: Large-scale absorption of electrolyte-free irrigating fluid during endoscopic surgery may result in a "transurethral resection syndrome." The severity of the syndrome can probably be modified by using mannitol 5% instead of the most widely used glycine 1.5%. METHODS: Seventeen pigs with a mean body weight of 22 (range 19-26) kg received an intravenous infusion of 100 mL kg(-1) h(-1) of either glycine 1.5% or mannitol 5% over 90 min. Central hemodynamics, whole-body and brain oxygen consumption, intracranial pressure, blood hemoglobin, and the sodium concentrations in serum and urine were monitored for 120 min. Selected measurements were made on 6 other pigs given mannitol 3% and in 2 controls not given any fluid. Morphological examinations of the hearts were conducted. RESULTS: Both glycine 1.5% and mannitol 5% transiently increased cardiac output, the aortic blood flow rate, and arterial pressures, but all of these parameters fell to below baseline after the infusions were ended. The intracranial pressure was lower (P < 0.05) and the oxygen consumption in the brain decreased (P < 0.001) during the infusion of mannitol 5%. Glycine 1.5% expanded the intracellular volume more than mannitol did (P < 0.002). Signs of myocardial damage were graded glycine 1.5% > mannitol 5% > mannitol 3%. CONCLUSIONS: Massive infusion of glycine 1.5% and mannitol 5% left the pigs in a hypokinetic hypotensive state. Glycine 1.5% increased the intracranial pressure and injured the myocardium more than mannitol 5%, which then seems to be a more appropriate irrigating fluid to use during endoscopic surgery.

Animals↗
PubMedDate not supplied

Intravenous infusion of glucose and the vasodilator sodium nitroprusside in combination with local hyperthermia: effects on tumour pH and tumour response in the BT4An rat tumour model.

The influence of sodium nitroprusside (SNP) induced hypotension on the extra-cellular tumour pH during local hyperthermia (HT), and on the cytotoxic effect of HT, was studied in the BT4An tumour transplanted to the hind limb of BD IX rats. Experiments with intravenous infusion of glucose before the HT/SNP combination were also performed. Local waterbath HT was given at 44 degrees C. Sodium nitroprusside was administered as a continuous i.v. infusion to lower the mean arterial blood pressure to 60 mmHg. Glucose was given as an i.v. infusion at a dosage of 4.8 g/kg body weight in 60 min before HT. Extracellular tumour pH was measured by a needle type glass electrode. The tumour pH fell from 7.19 to 6.81, on average, after 60 min HT. Sodium nitroprusside induced hypotension during HT did not increase the pH fall after 1 h HT, but the pH 60 min after discontinuation of HT was lower in this group than in the HT alone group. Pretreatment with glucose before HT gave similar results as the HT/SNP combination. When glucose was given before HT/SNP a highly relevant decline in tumour pH during HT from 7.22 to 5.95 was observed. In a separate tumour response experiment adding SNP to HT was found to prolong the tumour growth time. Pre-treatment with glucose before the HT/SNP combination prolonged the tumour growth time slightly. The applicability of this treatment protocol in the clinical treatment of patients is discussed.

Animals↗
PubMed1974

Continuous intravenous infusion of small doses of insulin in treatment of diabetic ketoacidosis.

Continuous intravenous infusion of small amounts of insulin has been used in the management of a series of patients with diabetic ketoacidosis. In 13 patients with a plasma glucose level on admission of 725 mg/100 ml (+/- 80 S.E. of mean) and an arterial pH of 7.07 +/- 0.05 a mean loading dose of 6.5 +/- 0.82 units of soluble insulin was administered intravenously, and thereafter a sustaining infusion of 6.5 +/- 0.82 U/hr was continued until ketosis was corrected and the plasma glucose fell below 300 mg/100 ml. The total insulin dose needed to achieve this was 39.2 +/- 6.6 units given over a 3 to 10-hour period. Plasma insulin was measured in patients who had not previously received insulin and the mean level at an infusion rate of 4 U/hr was 75.6 +/- 8.0 muU/ml. Plasma glucose fell at a regular rate of 101 +/- 11 mg/100 ml/hr, and ketosis improved in parallel. Plasma potassium was well maintained throughout treatment. This regimen of treatment was clinically effective and simple to follow.

Adolescent↗
PubMed1990

Effects of intravenous infusion of human prostate tissue substances in dogs.

Symptoms of postresection syndromes following transurethral prostatectomy have been associated with a transient increase in serum acid phosphatase due to intraoperative absorption of prostate tissue substances. Factors associated with postoperative syndromes include intraoperative absorption of irrigant solution, intraoperative blood loss, and intraoperative absorption of prostate tissue substance. An animal model was used in this study to determine the isolated physiologic effects of intravenous infusion of a saline prostate tissue extract using an infusion schedule comparable to that of transurethral prostate resection. Twenty-four animals received either normal saline infusion (control) or saline prostate tissue extract infusion (experimental). The experimental group showed a significant decrease in fibrinogen, platelet count, white blood count, activated clotting time, and plasma volume. These results suggest that the isolated effects of intravascular absorption of prostate tissue substances are due to disseminated intravascular coagulation, most likely resulting from tissue thromboplastin and activation of plasminogen.

Absorption↗
PubMed2006

Phase I trial of phenoxodiol delivered by continuous intravenous infusion in patients with solid cancer.

BACKGROUND: Phenoxodiol is a multi-pathway initiator of apoptosis with broad anti-tumor activity and high specificity for tumor cells. Its biochemical effects are particularly suited to reversal of chemo-resistance, and the drug is being developed as a chemo-sensitizer of standard chemotherapeutics in solid cancers. This phase I, single-center trial was conducted to test a continuous intravenous dosing regimen of phenoxodiol in patients with late-stage, solid tumors to determine toxicity, pharmacokinetics, and preliminary efficacy. METHODS: Phenoxodiol given by intravenous infusion continuously for 7 days on 14-day cycles was dose-escalated on an inter-patient basis at dosages of 0.65,1.3, 3.3, 20.0, and 27.0 mg/kg/day (three to four patients per stratum). Treatment cycles continued until disease progression. Toxicity was based on standard criteria; efficacy was based on changes in tumor burden (WHO); pharmacokinetic analysis was conducted on plasma samples at specified time points during treatment cycles. RESULTS: Nineteen heavily-pre-treated patients with solid tumors received a median of three cycles of treatment (range 1-13); two patients received >or= 12 cycles. No dose-limiting toxicities were encountered, with emesis and fatigue (one patient) and rash (one patient) the only significant toxicities. Stabilized disease was the best efficacy outcome, with one patient showing stable disease at 24 weeks. Pharmacokinetics suggested a linear relationship between dosage and mean steady-state plasma concentrations of phenoxodiol. CONCLUSION: A 7-day continuous infusion of phenoxodiol given every 2 weeks is well tolerated up to a dose of 27.0 mg/kg/day.

Adult↗